DESCRIPTION: UNAIDS has announced a goal of Getting to Zero New HIV infections and Secretary Clinton has announced a goal of an AIDS free generation. Completely eliminating new HIV infections may not be possible in any large population of persons at high risk for HIV, but combined prevention, including treatment as prevention (TasP) may permit getting very close to zero new HIV infections. Psychoactive drug use generates many impediments getting close to zero. Drug use can lead to HIV infection through both sharing injection equipment and through drug use related unsafe sexual behavior. Drug use may also interfere with accessing and adhering to antiretroviral therapy (ART). Psychoactive drug use is also strongly associated with higher rates of HIV infection among racial/ethnic minorities. In this research, we will examine whether combined prevention can get close to zero new HIV infections among injecting and non-injecting drug users in New York City, including whether getting close to zero can minimize racial/ethnic disparities. If combined prevention does lead to getting close to zero new infections drug users in NYC. This will require a) an analytic description of combined prevention, b) a clear conceptualization of getting close to zero, and c) new metrics and methods for assessing being close to zero. We will study getting close to zero new HIV infections for drug users in NYC through four specific aims: 1. Determine the extent to which combined prevention is getting close to zero for injecting related transmission of HIV in NYC. Develop new metrics for measuring a CtZ situation for injecting-related transmission and how racial/ethnic disparities might be minimized. 2. Conduct mathematical modeling, using biomarkers for high injecting risk (HCV infection) and high sexual risk (HSV-2 infection) and behavioral data to analyze HIV infection among PWID in terms of: 1) the PWID population as a whole, 2) disparities among major racial/ethnic groups, 3) sustainability for maintaining a CTZ situation with combined prevention, and 4) injecting related vs. sexual transmission of HIV among PWID. 3. Determine the extent to which combined prevention is reducing drug related sexual (DRS) transmission of HIV among non-injecting drug users (NIDUs) and PWID in NYC. Develop new metrics for measuring the potential for continuing sexual transmission and assess coverage of Treatment as Prevention (TasP) among NIDUs. Monitor trends in HSV-2 infection as a continuing driver of drug use sexual transmission. 4. Utilize geospatial analysis to characterize hotspots for continuing transmission of HIV among drug users in NYC, including potential geographic overlap between injecting related and sexual transmission of HIV, and racial/ethnic and HIV service characteristics of hotspots. We will accomplish these aims through interviews and HIV, HCV, and HSV-2 testing of 600 subjects per year and continuation of our long-standing collaborations with the NY City and State Health Departments.